A Novel Multi-Epitope-Based Peptide Vaccine for the Monkeypox Virus: A Reverse Vaccinology and Immunoinformatics Approach

Monkeypox (Mpox) is a zoonotic disease caused by the Monkeypox Virus (MPV), a member of the Orthopoxvirus genus of viruses. Although the virus typically results in mild symptoms, such as fever, muscle pain, and rash, its complications specially in vulnerable populations are severe and life-threatening. Currently, there is no specific treatment for Mpox, and available smallpox vaccines have undesirable adverse reactions, making further vaccine development imperative. The current study adopted a reverse vaccinology approach to design a Multi-Epitope based Subunit Vaccine (MEPV) against MPV. Four highly antigenic proteins, with no significant similarity with the homo sapiens proteome, were considered. All B and T cell (both major histocompatibility - MHC-I and MHC-II) epitopes were predicted, and non-toxic, soluble, non-allergenic, and antigenic epitopes were short-listed. The top eight epitopes were then selected from each of the MHC-I, MHC-II and B-cells epitopes. The selected epitopes demonstrated an overall coverage of 93.7<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">%</sup> of the world's population. The final vaccine construct contained 450 amino acid residues with high antigenic, immunogenic, non-toxic, and non-allergenic characteristics. The 3D structure of the vaccine was predicted by the I-Tasser online tool and refined using Galaxyweb server. Molecular docking analysis by Haddock indicated that the designed structure has good binding affinity for human pathogenic immune receptor TLR-3. Furthermore, the In-silico Immune Simulations confirmed that the proposed vaccine construct can elicit cell-based immune responses. Finally, Repeated-exposure simulations established rapid antigen clearance. Overall, our bioinformatics-based experiments suggest that the proposed MEPV could be a potential vaccine candidate to combat MPV, however, further in vitro cell culture and in vivo animal model experimental validations are needed prior to clinical trials.